Ruth B. Kundsin

Prospective Study of Chlamydia pneumoniae IgG Seropositivity and Risks of Future Myocardial Infarction

BACKGROUND Chlamydia pneumoniae has been hypothesized to play a role in atherothrombosis. However, prospective data relating exposure to Chlamydia pneumoniae and risks of future myocardial infarction (MI) are sparse. METHODS AND RESULTS In a prospective cohort of nearly 15 000 healthy men, we measured IgG antibodies directed against Chlamydia pneumoniae in blood samples collected at baseline from 343 study participants who subsequently reported a first MI and from an equal number of age- and smoking-matched control subjects who did not report vascular disease during a 12-year follow-up period. The proportion of study subjects with IgG antibodies directed against Chlamydia increased with age and cigarette consumption. However, prevalence rates of Chlamydia IgG seropositivity were virtually identical at baseline among men who subsequently reported first MI compared with age- and smoking-matched control subjects. Specifically, the relative risks of future MI associated with Chlamydia pneumoniae IgG titers >/=1:16, 1:32, 1:64, 1:128, and 1:256 were 1.1, 1.0, 1.1, 1.0, and 0.8, respectively (all probability values not significant). There was no association in analyses adjusted for other risk factors, evaluating early as compared with late events, or among nonsmokers. Further, there was no association between seropositivity and concentration of C-reactive protein, a marker of inflammation that predicts MI risk in this cohort. CONCLUSIONS In a large-scale study of socioeconomically homogeneous men that controlled for age, smoking, and other cardiovascular risk factors, we found no evidence of association between Chlamydia pneumoniae IgG seropositivity and risks of future MI.

Association of Ureaplasma urealyticum in the Placenta with Perinatal Morbidity and Mortality

Abstract We investigated the presence of ureaplasmas, mycoplasmas, chlamydiae, fungi, aerobic and anaerobic bacteria, and cytomegalovirus in fetal membranes and evaluated their association with perinatal morbidity and mortality. We cultured 801 placentas from three groups of subjects (144 who died in the perinatal period, 452 neonates admitted to the intensive-care unit, and 205 controls). Ureaplasma urealyticum, Mycoplasma hominis, or both were isolated from 21 per cent of placentas of premature and term infants who died in the perinatal period, 25 per cent of those admitted to intensive care, and 11 per cent of controls. Gestational age and birth weight were inversely related to isolation of ureaplasma, and chorioamnionitis was positively related to isolation. The presence of ureaplasmas in the placenta suggests the transcervical migration of these microorganisms from the lower genitourinary tract. These data show a strong association between ureaplasma infection of the placenta and low birth weight of ...

BASELINE IGG ANTIBODY TITERS TO CHLAMYDIA PNEUMONIAE, HELICOBACTER PYLORI, HERPES SIMPLEX VIRUS, AND CYTOMEGALOVIRUS AND THE RISK FOR CARDIOVASCULAR DISEASE IN WOMEN

Data from several studies have suggested that persons with coronary heart disease have an increased prevalence of chronic infection with such agents as Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, and cytomegalovirus (1). In addition, it has been hypothesized that infection may be a risk factor for acute coronary events (2). However, chronic infection is also more prevalent among smokers, elderly persons, and persons of lower socioeconomic status, and persons with a history of coronary disease may be more susceptible to subsequent infection. Therefore, it is uncertain whether the associations between infection and coronary heart disease that have been observed in retrospective and cross-sectional studies were caused by confounding or represent a result of ischemic heart disease rather than a cause (3). To resolve these issues, investigators have used prospective, controlled settingsin which exposure status can be ascertained before the onset of thrombosisto evaluate the theory that previous infection is related to atherosclerosis. The few reported prospective studies of C. pneumoniae (4-7), H. pylori (8-12), herpes simplex virus (13), and cytomegalovirus (13) have not provided strong evidence of an association; however, none of these studies evaluated multiple infectious exposures simultaneously. This is a potentially important issue because it has been hypothesized that a persons total burden of pathogens may be a critical factor in determining atherogenesis (14). In addition, the available prospective data were derived from studies that predominantly or exclusively evaluated men. To further investigate the theory that previous infection is related to atherothrombosis, we measured IgG antibody titers against C. pneumoniae, H. pylori, herpes simplex virus, and cytomegalovirus in baseline blood samples obtained from a large cohort of apparently healthy postmenopausal women who were followed prospectively for the occurrence of first cardiovascular events. We also related these antibody titers to plasma concentrations of high-sensitivity C-reactive protein, a marker of chronic inflammation that has previously been shown to predict coronary risk in this cohort (15). Methods We performed a nested casecontrol study among participants in the Womens Health Study, an ongoing primary prevention trial that enrolled 39 876 postmenopausal female health professionals with no history of myocardial infarction, stroke, or transient ischemic attack (16). Of women enrolled in the study, 28 311 (71%) provided baseline blood samples, which were frozen in liquid nitrogen until analysis. Case-patients were initially healthy Womens Health Study participants who provided a baseline blood sample and who subsequently reported a first cardiovascular event (myocardial infarction, stroke, cardiovascular death, or coronary revascularization procedure) during follow-up. Reported myocardial infarction was confirmed if review of hospital records met World Health Organization criteria and if the event was associated with characteristic electrocardiographic changes or elevated levels of cardiac enzymes. Reported stroke was confirmed if records showed a new neurologic deficit persisting for more than 24 hours; such records almost always included evidence from computed tomography or magnetic resonance imaging. Reported coronary angioplasty or coronary bypass surgery was confirmed by record review. Cardiovascular death was confirmed by autopsy reports, death certificates, and circumstances at the time of death. Controls were randomly selected from the pool of initially healthy Womens Health Study participants who remained free of cardiovascular disease during study follow-up and also provided a baseline blood sample. Two controls, matched for age (1 year) and smoking status (never, past, or current), were selected for each case-patient. Baseline plasma samples from case-patients and controls were thawed and assayed for IgG antibody titers against C. pneumoniae by using microimmunofluorescence techniques (6, 17). Similarly, enzyme-linked immunosorbent assays were used to qualitatively detect IgG antibodies to herpes simplex virus (Wampole Laboratories, Cranbury, New Jersey), cytomegalovirus (Gull Laboratories, Salt Lake City, Utah), and H. pylori (Wampole Laboratories) in baseline plasma samples. For each variable, samples from a case-patient and two matched controls were assayed as a group; samples from the case-patient were positioned randomly within the group to reduce interassay variability and to avoid systematic bias. All laboratory investigators were unaware of case-patient or control status at the time of IgG analysis. C-reactive protein levels were evaluated by using a high-sensitivity assay (Abbott Laboratories, Abbott Park, Illinois), as described elsewhere (15). We used conditional logistic regression analyses to test for evidence of an association between the presence of IgG antibodies at baseline and subsequent risk for cardiovascular events. A priori, we chose to evaluate the association between C. pneumoniae and subsequent risk across a series of IgG antibody titers (range,>1:16 to>1:128). The presence or absence of IgG seropositivity for herpes simplex virus, cytomegalovirus, and H. pylori was determined according to cut-points established by the assay manufacturers. Adjusted estimates of risk were computed after we controlled for baseline differences between case-patients and controls. To evaluate the theory that total infectious burden rather than any single IgG titer may be associated with risk, we further classified study participants as having zero, one, two, three, or four positive antibody titers. Because the number of study participants with zero positive titers at baseline was small (n=15), data from these participants and from participants with one positive titer were combined for analysis. Where applicable, tests for trend were used to evaluate evidence of increasing risk across increasing antibody titers (18). We also compared the distribution of C-reactive protein values for participants with two or more positive IgG antibody titers with the distribution of values for participants with zero or one positive IgG antibody titer. All P values are two-tailed. Results Among 122 case-patients, 85 myocardial infarctions or strokes occurred and 37 coronary revascularizations were performed. As is expected in a study of incident coronary events, case-patients were more likely than controls to have a history of hyperlipidemia (45.9% compared with 28.3%; P=0.001), hypertension (55.5% compared with 31.3%; P=0.001), and diabetes (9.8% compared with 2.1%; P=0.001) and to have a family history of premature coronary disease (21.3% compared with 12.7%; P=0.04). Case-patients also had a greater mean body mass index than controls (27.1 compared with 26.0 kg/m2; P=0.05). Because of matching, mean age (59.3 8.3 years) and smoking status (27.9% of participants currently smoked, 42.6% had never smoked, and 29.5% had smoked in the past) were identical in the case-patient and control groups. Exposure rates among controls were similar to those reported in previous studies; for example, 60% of controls had C. pneumoniae titers greater than 1:8 (1, 2). However, as shown in Table 1, the proportion of study participants with positive IgG titers was similar regardless of case-patient or control status. For example, the crude rate ratios for future cardiovascular events in women with C. pneumoniae titers 1:16, 1:32, 1:64, and 1:128 were 1.1, 1.1, 1.1, and 1.0, respectively (P>0.2 overall) (Table 1). Similarly, the crude rate ratios for future cardiovascular events associated with baseline seropositivity to H. pylori, herpes simplex virus, and cytomegalovirus were 0.9, 1.2, and 0.9, respectively (P>0.2 overall). As shown in Figure 1, these point estimates did not change after adjustment for baseline differences in hyperlipidemia, hypertension, exercise frequency, body mass index, diabetes, and family history of premature coronary artery disease. Table 1. Rate Ratios for Future Cardiovascular Events among Apparently Healthy Women, according to Baseline IgG Antibody Status Figure 1. Adjusted rate ratios for future cardiovascular events among apparently healthy women, according to the presence of baseline IgG antibody titers against Chlamydia pneumoniae , herpes simplex virus, cytomegalovirus, and Helicobacter pylori ( top ) and the number of positive baseline IgG titers present ( bottom ). To evaluate the theory that total pathogen burden might be associated with increased risk, we stratified patients into four groups according to the total number of positive titers observed in a given case-patient or control. As shown in Table 2, the rate ratios for future cardiovascular events in women with zero or one, two, three, or four positive IgG titers were 0.9, 1.1, 1.0, and 1.0, respectively (P>0.2 overall). Similarly, in analyses that evaluated evidence of trend across these four groups, little evidence supported an association (P>0.2 for trend). As shown in Figure 1, adjustment for baseline differences between case-patients and controls had little or no effect on these results. Table 2. Rate Ratios for Future Cardiovascular Events among Apparently Healthy Women, according to the Total Number of IgG Antibody Titers Present in a Given Study Participant Previously obtained data from this cohort indicate that median C-reactive protein levels are significantly higher in participants who subsequently reported coronary events than in controls (6.45 compared with 3.75 mg/L; P<0.001); this suggests that chronic low-grade inflammation is a marker of risk in this group of women (15). However, when we compared participants with and those without positive IgG antibody titers, the distribution of C-reactive protein levels was similar in isolated analyses limited to each pathogen, in analyses evaluating total pathogen burden (Figure 2), and in analy

Strain of Mycoplasma Associated with Human Reproductive Failure

A strain of mycoplasma not previously described has been isolated from the chorion, decidua, and amnion of a patient who sustained a spontaneous abortion during the middle trimester. The fetal membranes exhibited an inflammatory reaction, but no evidence of other infectious agents, bacterial or viral, was noted. The T strain identified is not a classical mycoplasma; it differs in growth and nutritional requirements from the T strains previously characterized.

Ureaplasma urealyticum infection of the placenta in pregnancies that ended prematurely

Objective To investigate the relationship between Ureaplasma urealyticum infection of the placenta and premature onset of labor. Methods We studied 647 pregnancies that resulted in the live birth of an infant weighing less than 1501 g. The chorionic surface of the placenta was cultured for U urealyticum, Mycoplasma hominis, and group B streptococci. Results The rate of ureaplasma isolation increased with increasing interval between rupture of membranes and delivery. When analyses were limited to the 96 singleton pregnancies that ended within 1 hour of rupture of membranes and before the 29th week of gestation, U urealyticum was prominently associated with an increased risk of premature onset of labor (P = .008 unadjusted, and P = .05 when adjustment was made for all potential confounders). Ureaplasma infection rate was lowest in pregnancies terminated because of severe maternal preeclampsia or progressive fetal growth restriction. Conclusion Ureaplasma ureaplasma urealyticum infection is associated with premature onset of labor and with increasing duration of time between rupture of membranes and delivery. Eradication of ureaplasmas from the urogental tract of women and their partners, ideally before conception, should be considered.

Prosthetic valve endocarditis caused by Mycoplasma hominis

I nfective endocarditis accounts for 0.1 to 0.5 percent of hospital admissions. In the majority of cases, a pathogenic organism can be identified from blood cultures; however, in 3 to 30 percent of cases, an organism cannot be identified from the blood [l]. In these cases, special procedures such as culturing the blood for a longer period of time or with special medium or culturing the cardiac valve may reveal fastidious organisms. These include nutritionally deficient streptococci, slow-growing gram-negative bacilli, brucella, anaerobes, corynebacteria, mycobacteria, fungi, and yeast. Serology may be required for a diagnosis of Q fever or chlamydia endocarditis. Finally, in some cases, an organism cannot be identified despite multiple attempts using culture and serology. We recently cared for a patient with infective endocarditis involving prosthetic valves. Numerous blood cultures were negative and at thoracotomy microabscesses were seen on the aortic annulus. Two cultures from the mitral annulus grew Mycoplasma hominis. Since mycoplasmas have not previously been isolated from patients with endocarditis, we present this case and suggest that the organism be considered in the differential diagnosis of culture-negative endocarditis.

ULTRAVIOLET RADIATION AND REDUCTION OF DEEP WOUND INFECTION FOLLOWING HIP AND KNEE ARTHROPLASTY

Deep wound infection as a complication of clean surgery is not a new problem and it is not a problem solely limited to the specialty of orthopaedic surgery. It has been a concern of surgeons since the beginning of the surgical era and although tremendous strides have been made in prevention and treatment, the problem is still with us and will remain. The issue forced itself upon the orthopaedic surgeon with renewed vigor in the late 1960s and early 1970s with the advent of total joint replacement surgery and its unique success in dealing with the problems imposed by arthritis of the weight-bearing joints. In a very few years, surgeons all over the world learned the techniques and applied them to thousands of patients. By the mid-1970s, it is estimated that in the United States, 100,000 patients annually were undergoing total hip replacement arthroplasty, with many more thousands having replacement surgery of the knee, ankle, shoulder, elbow, wrist, and hand. If we assume a deep wound infection rate of 1 percent, an exceedingly conservative figure, the number of patients developing wound infection of the hip would be 1,000 per year and the best evidence suggests that the infection rate is at least twice this. With the price of a hospital bed in many major medical institutions in excess of

Chromosomal aberrations induced by T strains mycoplasmas.

200 per day and the length of hospitalization for treatment of these infections running from 4 weeks to 6 months, the cost of dealing with them, let alone the misery and suffering accruing to the patients, is staggering, averaging over

New technic for detection of bacterial contamination in a blood bank using plastic equipment.

20,000 per patient and often exceeding

Tetracycline-Resistant T-Mycoplasmas (Ureaplasma urealyticum) from Patients with a History of Reproductive Failure

100,000.’ The patient whose joint replacement prosthesis must be removed in order to control infection is often left worse off than prior to surgery. The term ‘refined clean surgery’ is usually applicable to joint replacement procedures. The joints rarely have been the site of previous surgery or infection and contrary to the situation in general surgery, regions such as the gastrointestinal, genitourinary, and respiratory tracts are not entered. Endogenous bacteriologic soiling is an unlikely accompaniment of the procedure. Contamination must, therefore, come from without, the possible exception being a bacteremia from manipulations of the mouth and respiratory tract that accompany intubation as a necessary part of anesthetic management. The procedure is elective. Historically the orthopaedic community came by its concern quite naturally. The first uniformly successful method of managing the painful arthritic hip was developed by M. N. Smith-Petersen in the late 1930s and called mold arthroplasty. The femoral head and acetabulum were reshaped from deformed contours to round, matching, congruous surfaces. Between these, a nonperishable barrier was interposed of chrome-cobalt-molybdenum alloy to guide the repair process. Over a period of months a fibro-cartilaginous covering of the bone developed.